The studies supported by this grant deal with three major areas of lipid and lipoprotein metabolism: 1) Fatty acid binding protein (FABP). We are continuing to examine the function of FABP, a 12,000 M.W. soluble protein present in many mammalian tissues which transport and/or utilize fatty acids, including intestine, liver, myocardium, kidney and adipose. Our recent isolation of the protein from rat intestine and demonstration of its functional significance in in vitro studies provide the base for further experiments designed to elucidate more definitively its role in cellular fatty acid metabolism. We are in the process of isolating FABP from human intestine. 2) Intestinal metabolism of endogenous lipids and lipoproteins. We have recently conducted studies demonstrating the intestinal uptake and metabolism of plasma FFA, and an apparent intracellular compartmentation of fatty acids which enter the intestinal absorptive cell from luminal and basal (plasma) surfaces. We expect to continue our studies with the intention of defining the basis for this compartmentation and the possible implications it may have for fatty acid metabolism in other mammalian cells. The qualitative and quantitative significance of endogenous intestinal lipoprotein production will continue to be explored. 3) Studies of bile secretion in cholestasis. Our studies in this area will continue and are expected to expand into a more comprehensive examination of the mechanism(s) by which bile acids and lipids are secreted into bile, and of the relationship between this process and of tissue bile acid levels to cholestasis. Our studies will employ, in part, a recently described model of selective biliary obstruction which provides us with the opportunity of studying obstructed and non-obstructed liver tissue in the same animal under conditions of experimental cholestasis. BIBLIOGRAPHIC REFERENCES: Ockner, R.K. and Manning, J.A. Fatty acid binding protein: role in esterification of absorbed long chain fatty acid in rat intestine. J. Clin. Invest., September, 1976. Jones, A.K., Schmucker, D.L., Adler, R.D., Ockner, R.K. and Mooney, J.S. A quantitative analysis of hepatic ultrastructure in rats after selective biliary obstruction. Second International Gstaad Symposium, Gstaad, Switzerland, 1975.